First-principles modeling of complexation of anticancer antibiotics with fullerene (C60) nanocage: Probing non-covalent interactions by vibrational and electronic spectroscopy

Abstract

A critical assessment of binding energetics for the non-covalent conjugation of drug molecules with nanocarriers is a cornerstone problem in chemical physics due to the omnipresence of many-body van der Waals (vdW) interactions and thereby entailing a meaningful theoretical approach to decipher the origin of surface-molecule interactions at the nanoscale. Fullerene-C60, which possesses a unique spherical structure with a strong apolar character, promised to serve as drug delivery scaffolds through covalent or non-covalent interactions with the bioactive moiety. Herein, we have explored the binding characteristics of three anticancer antibiotics viz. Doxorubicin, Mitomycin, and Epirubicin with C60 nanocage by performing density functional theory (DFT) based calculations. The essence of surface-molecule interactions is derived from the DFT-based methods in conjunction with semiclassical treatments of the dispersion interaction (D3 approach) and semilocal density functional (M06–2X). Stabilities and reactivities of the drug adsorbed fullerene-C60 complexes are assessed in both the aqueous and protein core environment. The calculated IR stretching frequencies, Raman scattering activities, optical absorption coefficients, global chemical reactivity descriptors as well as thermochemical properties are subsequently analyzed to reveal the nature of the noncovalent interactions between C60 and antineoplastic therapeutics.